Activation of group I mGluRs elicits different responses in murine CA1 and CA3 pyramidal cells.

The group I metabotropic glutamate receptor agonist DHPG has been shown to produce two major effects on CA3 pyramidal cells at rest: a reduction in the background conductance and an activation of a voltage-gated inward current (I(mGluR(V))). Both effects contribute to depolarising CA3 pyramidal cells and the latter has been implicated in eliciting prolonged epileptiform population bursts. We observed that DHPG-induced depolarisation was smaller in CA1 pyramidal cells than in CA3 cells. Voltage clamp studies revealed that while DHPG elicited I(mGluR(V)) in CA3 pyramidal cells, such a response was absent in CA1 pyramidal cells. Both mGluR1 and mGluR5 have been localised in CA3 pyramidal cells, whereas only mGluR5 has been detected in CA1 pyramidal cells. Using mGluR1 knockout mice, we evaluated whether the absence of an I(mGluR(V)) response can be correlated with the absence of mGluR1. In these experiments, DHPG failed to elicit I(mGluR(V)) in CA3 pyramidal cells. This suggests that the smaller depolarising effects of DHPG on wild-type CA1 pyramidal cells is caused, at least in part, by the absence of I(mGluR(V)) in these cells and that the difference in the responses of CA1 and CA3 cells may be attributable to the lack of mGluR1 in CA1 pyramidal cells.